Clinical Trial Results:
Sclero XIII: A phase II ,double-blind, randomized, placebo-controlled study to investigate pharmacokinetics (PK), safety and efficacy of intravenous factor XIII treatment in patients with systemic sclerosis
Summary
|
|
EudraCT number |
2014-001101-40 |
Trial protocol |
GB |
Global end of trial date |
06 Sep 2018
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
15 Dec 2022
|
First version publication date |
19 Dec 2019
|
Other versions |
v1 |
Version creation reason |
|
Summary report(s) |
Sclero XIII study report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
13/0417
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02551042 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IRAS: 150751 | ||
Sponsors
|
|||
Sponsor organisation name |
University College London, Joint Research Office
|
||
Sponsor organisation address |
149 Tottenham Court Road, London, United Kingdom,
|
||
Public contact |
Prof Christopher Denton, University College London, +44 02073177544, c.denton@ucl.ac.uk
|
||
Scientific contact |
Prof Christopher Denton, University College London, +44 02073177544, c.denton@ucl.ac.uk
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
30 Sep 2019
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
06 Sep 2018
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
06 Sep 2018
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
1.To identify any effects of factor XIII treatment on clinical manifestations of Sleroderma (SSc)
2.To investigate factor XIII safety
3.To measure individual factor XIII levels in patients with SSc
4.To measure the effects of factor XIII treatment on factor XIII PK parameters.
5.To explore effects of factor XIII on thrombospondin expression
|
||
Protection of trial subjects |
The study involved an initial PK open label arm to assess the safety and tolerability of the IMP in the patient population as well as generating a dosing algorithm that would be used in the double blind, randomized placebo-controlled treatment arm. This was built into the study in order to to minimize safety issues .
|
||
Background therapy |
Immunosuppressants such as mycophenolate, cyclophosphamide, and methotrexate are prescribed to manage disease symptoms as there is currently no approved medication. | ||
Evidence for comparator |
This is a phase II, double-blind, randomised, placebo-controlled study to investigate the pharmacokinetics, safety and efficacy of intravenous factor XIII treatment in patients with systemic sclerosis, as there is no approved drug for Diffuse Systemic Sclerosis (DcSSC) a placebo arm is the relevant comparator | ||
Actual start date of recruitment |
09 Aug 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United Kingdom: 26
|
||
Worldwide total number of subjects |
26
|
||
EEA total number of subjects |
26
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
19
|
||
From 65 to 84 years |
7
|
||
85 years and over |
0
|
|
|||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||
Recruitment details |
Recruitment window was 24/11/2015 to 22/01/2018 | ||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||
Screening details |
PK arm- 8 participants were screened and randomized Treatment arm- 22 participants were screened and 18 randomized. There were 4 screen failures and 1 withdrawal | ||||||||||||||||||||
Period 1
|
|||||||||||||||||||||
Period 1 title |
Overall Trial (overall period)
|
||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||
Blinding implementation details |
Both the investigators and subject were blinded to treatment group allocation. Only the pharmacy staff and designated unblinded nurse were unblinded in order for them to review study participants Factor XIII levels.
|
||||||||||||||||||||
Arms
|
|||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||
Arm title
|
Active treatment | ||||||||||||||||||||
Arm description |
6 participants with diffuse and 6 with limited SSc were randomly allocated to receive active treatment; | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Fibrogammin®P, coagulation factor XIII concentrate (Human)
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Solution for injection/infusion
|
||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||
Dosage and administration details |
Individual dosing to 220% of normal every 14 days for 24 weeks. FXIII levels to be measured before and after injection
|
||||||||||||||||||||
Arm title
|
Placebo | ||||||||||||||||||||
Arm description |
3 participants with diffuse SSc and 3 with limited SSc were randomly allocated to receive placebo. | ||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||
Investigational medicinal product name |
Sodium Chloride, 0,9%
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Solution for solution for infusion
|
||||||||||||||||||||
Routes of administration |
Intravascular use
|
||||||||||||||||||||
Dosage and administration details |
Standardised placebo administration every 14 days for 24 weeks total
|
||||||||||||||||||||
Arm title
|
PK arm | ||||||||||||||||||||
Arm description |
4 patients with limited and 4 patients with diffuse systemic sclerosis received a single dose of factor XIII and levels were monitored over a six-week period | ||||||||||||||||||||
Arm type |
PK safety | ||||||||||||||||||||
Investigational medicinal product name |
Fibrogammin®P, coagulation factor XIII concentrate (Human)
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Solution for injection/infusion
|
||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||
Dosage and administration details |
Participants will receive a single intravenous injection of factor XIII concentrate either 20 or 40 IU/kg, depending on starting levels. Participants with starting levels great than or equal to 90% of normal will receive 20 IU/kg. Participants with starting levels less than 90% of normal will receive 40 IU/kg
|
||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Trial
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
PK
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
(PK) phase of the trial aimed to assess the safety and tolerability of the IMP in the SSc patient. It also aimed to generate data to produce a dosing algorithm that could be used in the Treatment Phase.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Active Treatment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
12 patients on active treatment, 6 with limited disease and 6 with diffuse disease
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
6 participants on Placebo, 3 with limited disease and 3 diffuse
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Active treatment
|
||
Reporting group description |
6 participants with diffuse and 6 with limited SSc were randomly allocated to receive active treatment; | ||
Reporting group title |
Placebo
|
||
Reporting group description |
3 participants with diffuse SSc and 3 with limited SSc were randomly allocated to receive placebo. | ||
Reporting group title |
PK arm
|
||
Reporting group description |
4 patients with limited and 4 patients with diffuse systemic sclerosis received a single dose of factor XIII and levels were monitored over a six-week period | ||
Subject analysis set title |
PK
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
(PK) phase of the trial aimed to assess the safety and tolerability of the IMP in the SSc patient. It also aimed to generate data to produce a dosing algorithm that could be used in the Treatment Phase.
|
||
Subject analysis set title |
Active Treatment
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
12 patients on active treatment, 6 with limited disease and 6 with diffuse disease
|
||
Subject analysis set title |
Placebo
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
6 participants on Placebo, 3 with limited disease and 3 diffuse
|
|
||||||||||
End point title |
Skin involvement | |||||||||
End point description |
Skin involvement measured with modified Rodnan skin score
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Baseline to 24 weeks
|
|||||||||
|
||||||||||
Attachments |
Untitled (Filename: Capture.PNG) |
|||||||||
Statistical analysis title |
Skin Involvement | |||||||||
Comparison groups |
Placebo v Active Treatment
|
|||||||||
Number of subjects included in analysis |
18
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority [1] | |||||||||
P-value |
≤ 0.05 | |||||||||
Method |
ANCOVA | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
Notes [1] - Please see attached chart |
|
||||||||||
End point title |
Raynaud condition score | |||||||||
End point description |
Raynaud condition score
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Baseline to week 24
|
|||||||||
|
||||||||||
Attachments |
Untitled (Filename: Capture.PNG) |
|||||||||
Statistical analysis title |
Raynauds condition score | |||||||||
Comparison groups |
Active Treatment v Placebo
|
|||||||||
Number of subjects included in analysis |
18
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
≤ 0.05 | |||||||||
Method |
ANCOVA | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Confidence interval |
|
||||||||||||||||
End point title |
Pulmonary function [2] | |||||||||||||||
End point description |
||||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From baseline to week 24
|
|||||||||||||||
Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analyses for this end point. |
||||||||||||||||
|
||||||||||||||||
Attachments |
Secondary endpoints |
|||||||||||||||
Statistical analysis title |
Pulmonary function | |||||||||||||||
Comparison groups |
Placebo v Active treatment
|
|||||||||||||||
Number of subjects included in analysis |
18
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority [3] | |||||||||||||||
P-value |
≤ 0.05 | |||||||||||||||
Method |
ANCOVA | |||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||
Confidence interval |
||||||||||||||||
Notes [3] - Descriptive analysis |
|
||||||||||
End point title |
Hand function measured with Cochin hand function | |||||||||
End point description |
||||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline to 24 weeks
|
|||||||||
|
||||||||||
Attachments |
Untitled (Filename: Secondary endpoints.PNG) |
|||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
• Quality of life measured with SF36 quality of life questionnaire | |||||||||
End point description |
||||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline to 24 weeks
|
|||||||||
|
||||||||||
Attachments |
Untitled (Filename: Secondary endpoints.PNG) |
|||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Prevention of new DU (Digital Ulcers) | |||||||||
End point description |
||||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline to 24 weeks
|
|||||||||
|
||||||||||
Attachments |
Untitled (Filename: Secondary endpoints.PNG) |
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline to end of study
|
||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety and tolerability of Factor XIII assessed by physical examination (including digital ulcer characterization),Vital signs (heart rate, blood pressure, pulse, body weight) and Clinical laboratory parameters. Study doctor also enquired about adverse events
at every study visit between baseline and end of study.
|
||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19
|
||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PK arm
|
||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Active Treatment
|
||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
07 Jun 2016 |
Main updates to Protocol detailed below:
-Addition of routine blood tests
-Clarification in urine pregnancy tests "to women of childbearing potential"
-Clarification to avoid unnecessary capillaroscopy testing.
-Patients will be monitored for a minimum of one house after dosing.
-Updates to Concomitant medications to ensure patient safety i.e use of Bosentan included as an exclusion criteria
- Dosing algorithm for treatment phase explained in detail
-Update to dose modifications |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
As this was a small trial, all analysis is descriptive and no robust conclusion about efficacy can be drawn from the data. therefore this study confirms feasibility of recruitment to the designed trial and provides a platform for future studies. |